6-43582370-TTTTG-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_006502.3(POLH):c.54_57del(p.Val19LysfsTer10) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
POLH
NM_006502.3 frameshift
NM_006502.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.78
Genes affected
POLH (HGNC:9181): (DNA polymerase eta) This gene encodes a member of the Y family of specialized DNA polymerases. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases. However, it accurately replicates UV-damaged DNA; when thymine dimers are present, this polymerase inserts the complementary nucleotides in the newly synthesized DNA, thereby bypassing the lesion and suppressing the mutagenic effect of UV-induced DNA damage. This polymerase is thought to be involved in hypermutation during immunoglobulin class switch recombination. Mutations in this gene result in XPV, a variant type of xeroderma pigmentosum. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 41 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-43582370-TTTTG-T is Pathogenic according to our data. Variant chr6-43582370-TTTTG-T is described in ClinVar as [Pathogenic]. Clinvar id is 5885.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLH | NM_006502.3 | c.54_57del | p.Val19LysfsTer10 | frameshift_variant | 2/11 | ENST00000372236.9 | |
POLH | NM_001291970.2 | c.54_57del | p.Val19LysfsTer10 | frameshift_variant | 2/11 | ||
POLH | NM_001291969.2 | c.-17-634_-17-631del | intron_variant | ||||
POLR1C | NM_001318876.2 | c.945+53102_945+53105del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLH | ENST00000372236.9 | c.54_57del | p.Val19LysfsTer10 | frameshift_variant | 2/11 | 1 | NM_006502.3 | P1 | |
POLH | ENST00000372226.1 | c.54_57del | p.Val19LysfsTer10 | frameshift_variant | 2/11 | 1 | |||
POLH | ENST00000443535.1 | c.-49-634_-49-631del | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Xeroderma pigmentosum variant type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 17, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.